Concentration measuring instrument, concentration measuring contact apparatus, concentration measuring calculating apparatus, and concentration measuring method

ABSTRACT

To provide a concentration measuring method which enables a stable and highly accurate concentration measurement while avoiding the step of making a background measurement. 
     The concentration measuring apparatus includes: a concentration measuring contact that is brought into contact with a subject of measurement; a light source that emits light and enters the light into the concentration measuring contact; a polarizer that takes out p-polarized and s-polarized light components from the light which is passed through the concentration measuring contact into the subject of measurement, transmitted in the subject of measurement, and returned to the concentration measuring contact; a photodetector that determines at least the quantities of the p-polarized and s-polarized light components taken out by the polarizer; and calculating means that calculates the concentration of a specific component contained in the subject of measurement based on the determined results.

This application is a U.S. national phase application of PCTisternational application PCT/JP03/02534.

TECHNICAL FIELD

The present invention relates to a concentration measuring instrument,concentration measuring contact apparatus, concentration measuringcalculating apparatus, and concentration measuring method of measuringconcentrations of glucose, cholesterol, ethanol, etc.

BACKGROUND ART

A variety of methods have been proposed which measure specificcomponents in specimens, particularly in living bodies and solutionsusing an attenuated total reflectance (hereinafter referred to as ATR)measuring instrument.

For example, in Japanese Patent Laid-Open No. 9-113439, there isproposed a method of measuring the blood sugar level using a transparentATR device 51 having a pair of parallel reflecting surfaces opposingeach other in which measurement is made with upper and lower lips 52, asa specimen, brought into tight contact with the ATR device 51, as shownin FIG. 7. According to this method, the measurement of the blood sugarlevel is made through the following procedures: inserting an ATR device51 between upper and lower lips, and getting the same to be hold firmlyby the lips; entering light into the ATR device 51 so that the light isallowed to undergo total reflection repeatedly at the interface betweeneach reflection surface of the ATR device 51 and the lips 52, as shownby the broken line in FIG. 7; and analyzing the light that oozes out ofthe ATR device 51. The entire disclosure of Japanese Patent Laid-OpenNo. 9-113439 is incorporated herein by reference in its entirety.

In BME, Vol. 5, No. 8 (Japan ME Society, 1991), there is proposed amethod which measures the blood sugar level, the concentration ofethanol in blood, etc. using an ATR device made up of ZnSe opticalcrystal etc. In the method, measurements are made through the followingprocedures: bringing the ATR device into tight contact with lip mucosa;entering a laser light with a wavelength of 9 to 11 microns into the ATRdevice and allowing the light to undergo multiple reflection inside theATR device; and analyze the absorbed and scattered light. The entiredisclosure of BME, Vol. 5, No. 8 (Japan ME Society, 1991) isincorporated herein by reference in its entirety.

According to this method, concentrations of specific components such asglucose, ethanol and cholesterol can be measured non-invasively and inreal time. This method is to apply evanescent light (known as ooze-outlight) to a quantitative analysis. Only a very small quantity of thelight traveling in the ATR device actually enters lips, and the lighthaving entered the lips is affected by components in the body fluidexisting in the lips.

For example, in glucose, its light absorption peaks at a wave number of1080 cm⁻¹; therefore, when applying light with the above wave number toa living body, the quantity of the light absorption of glucose changesdepending on the glucose concentration in the living body. Accordingly,if the quantity of the light returned from the living body is measured,the change in quantity of the light absorption of a component in bodyfluid with change in the concentration of the component can be detected,in other words, the concentration of the component can be obtained.

When measuring the absorbance of a substance surface with an ATRmeasuring instrument and calculating the concentration of the same usingthe measured absorbance, the measuring method shown in FIG. 8 has beencommonly used.

First, in the background measuring step, the measurement of backgroundis made by entering light emitted by a light source into the ATR device,carrying out spectrometry of a reference, such as air or deionizedwater, while keeping the ATR device out of contact with a sample as asubject of measurement, and storing the measured results in a memory(S4). The reasons for the background measurement are to correct thewavelength characteristics of a light source and a photodetector and toensure an accurate absorbance measurement or concentration calculationeven after their characteristics have changed with time.

Then, the sample as a subject of measurement is set so that it comes incontact with the ATR device (S5) and measurement is made for the sample(S6).

Calculation is carried out according to the following equation, Log₁₀(Ib/Im), where Ib represents a detected signal from the photodetector atthe time of background measurement and Im a detected signal from thephotodetector at the time of measurement for the sample (S7). Thecalculated value is commonly referred to as absorbance. Since absorbancecorrelates with concentration of a specific components in a sample, if acalibration curve of absorbance and concentration is prepared inadvance, the concentration of a specific component in the sample can beestimated from the calculated absorbance.

The conventional ATR measuring instruments described above, however,have the following problems.

When making measurement of a sample after a certain length of time haselapsed since the completion of background measurement, the intensity ofthe light source and the sensitivity of the photodetector have changeddelicately, which has made accurate measurement of the sample difficult.

Further, when measuring the spectral characteristics of a sample, inorder to make the measurement accurate, it is necessary to set thecontact position and the contact area, where the sample and the ATRdevice are in contact with each other, just the same as those at thetime of background measurement. However, such setting has been difficultto perform accurately; as a result, the obtained accuracy of measurementhas not been satisfactory. Particularly when the sample has been aliving body, it has been difficult to accurately position the sample andthe ATR device at the time of measurement.

DISCLOSURE OF THE INVENTION

The present invention has been made in the light of the above describedproblem. Accordingly, the object of the invention is to provide aconcentration measuring apparatus, concentration measuring contactapparatus, concentration measuring calculating apparatus, andconcentration measuring method which enables stable and highly accurateconcentration measurement while avoiding the step of making backgroundmeasurement.

To solve the above problems, a first aspect of the present invention isa concentration measuring apparatus, comprising:

a concentration measuring contact (2) that is brought into contact witha subject of measurement;

a light source that emits light and enters the light into theconcentration measuring contact;

a polarizer that takes out p-polarized and s-polarized light componentsfrom the light which is passed through the concentration measuringcontact into the subject of measurement, transmitted in the subject ofmeasurement, and returned to the concentration measuring contact;

a photodetector that determines at least the quantities of thep-polarized and s-polarized light components taken out by thephotodetector; and

calculating means that calculates the concentration of a specificcomponent contained in the subject of measurement based on thedetermined results.

A second aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the calculating means calculates the concentration of thespecific component utilizing correspondence information obtained inadvance that allows the determined results to have a one-to-onecorrespondence with the concentrations of the specific component.

A third aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the concentration measuring contact is an attenuated totalreflection device and the light entered into the subject of measurementis evanescent light that oozes from the attenuated total reflectiondevice.

A fourth aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the subject of measurement is a living body tissue and thespecific component is glucose, ethanol, cholesterol or a derivative ofcholesterol.

A fifth aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the calculating means carries out calculation according to theequation, log10 (Is/Ip) or log10 (Ip/Is), where Ip represents themeasured value of the quantity of the p-polarized light component and Isrepresents the measured value of the quantity of the s-polarized lightcomponent, and obtains the concentration of the specific component basedon the calculated value.

A sixth aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the calculating means carries out calculation according to theequation, Ip/Is or Is/Ip, where Ip represents the measured value of thequantity of the p-polarized light component and Is represents themeasured value of the quantity of the s-polarized light component andobtains the concentration of the specific component based on thecalculated value.

A seventh aspect of the present invention is the concentration measuringapparatus according to the first aspect of the present invention,wherein the photodetector measures the quantities of the p-polarizedlight component and the s-polarized light component alternately at leastone time or more for each,

the calculating means (8) selects, from among the measured valuesmeasured by the photo detector, the measured value of Ip, the quantityof the p-polarized light component, and the measured value of Is, thequantity of the s-polarized light component, the values being obtainedat the respective measurement time points in immediate proximity to eachother, carries out calculation using the selected Ip and Is values, andobtains the concentration of the specific component based on thecalculated value.

The eighth aspect of the present invention is also a concentrationmeasuring method of measuring a specific component contained in asubject of measurement including:

a contacting step of bringing the concentration measuring contact intocontact with the subject of measurement;

a light entering step of entering light into the concentration measuringcontact;

a measuring step of measuring at least the quantities of the p-polarizedlight component and the s-polarized light component of the light that ispassed through the concentration measuring contact into the subject ofmeasurement, transmitted in the subject of the measurement, and returnedto the concentration measuring contact; and

a calculating step of calculating the concentration of the specificcomponent contained in the subject of measurement based on thedetermined results in the measuring step.

The ninth aspect of the present invention is also a concentrationmeasuring contact apparatus including:

a concentration measuring contact (2) that is brought into contact witha subject of measurement;

a light source (1) that emits light and enters the light into theconcentration measuring contact (2);

a polarizer (7) that takes out p-polarized and s-polarized lightcomponents of the light that is passed through the concentrationmeasuring contact (2) into the subject of measurement, transmitted inthe subject of measurement, and returned to the concentration measuringcontact (2); and

a photodetector (6) that determines at least the quantities of thep-polarized light component and the s-polarized light component takenout by the polarizer, wherein the concentration of a specific componentcontained in the subject of measurement is calculated by calculatingmeans based on the determined results.

The tenth aspect of the present invention is also a concentrationmeasuring calculating apparatus including:

calculating means (8) that calculates the concentration of a specificcomponent contained in a subject of measurement based on determinedresults obtained by a concentration measuring contact apparatus whichincludes:

a concentration measuring contact (2) that is brought into contact withthe subject of measurement;

-   -   a light source (1) that emits light and enters the light into        the concentration measuring contact (2);

a polarizer (7) that takes out p-polarized and s-polarized lightcomponents of the light that is passed through the concentrationmeasuring contact (2) into the subject of measurement, transmitted inthe subject of measurement, and returned to the concentration measuringcontact (2); and

a photodetector (6) that determines at least the quantities of thep-polarized light component and the s-polarlized light component takenout by the polarizer. The present invention may be the third invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic diagram of a concentration measuring contact whichis used in a concentration measuring method of measuring a specificcomponent contained in a subject of measurement in accordance with oneembodiment of this invention;

FIG. 2 is a flow diagram showing a measurement flow of the concentrationmeasuring method of measuring a specific component in a subject ofmeasurement in accordance with one embodiment of this invention;

FIG. 3 illustrates characteristic curves showing incident light wavenumber dependency of the value, Ip/Is, obtained by the concentrationmeasuring method of measuring a specific component in a subject ofmeasurement in accordance with the same embodiment of this invention;

FIG. 4 is a graph showing the relation between the value, Ip/Is, and theglucose concentration obtained by the concentration measuring method ofmeasuring a specific component in a subject of measurement in accordancewith the same embodiment of this invention;

FIG. 5 is a graph showing the relation between the value, Ip/Is, and theglucose concentration in accordance with the same embodiment of thisinvention which are obtained using a light source whose quantity oflight is decreased by 10% compared with that of the light source withwhich the relation between the value, Ip/Is, and the glucoseconcentration shown in FIG. 4 is obtained;

FIG. 6 is a schematic diagram of a concentration measuring contact whichis used in a concentration measuring method of measuring a specificcomponent contained in a subject of measurement in accordance with thesame embodiment of this invention, in which an interference filter typeof polarizer is used as a polarizer;

FIG. 7 is a schematic diagram showing a concentration measuring methodwhich uses the conventional ATR device; and

FIG. 8 is a flow diagram showing a measurement flow of the conventionalconcentration measuring method.

DESCRIPTION OF SYMBOLS

-   1 Light Source-   2 Concentration Measuring Contact-   3 Light Input Portion-   4 Contact Portion-   5 Light Output Portion-   6 Photodetector-   7 Polarizer-   51 ATR device-   52 Lips

Best Mode for Carrying Out the Invention

In the following, embodiments of the present invention will be describedwith reference to the accompanying drawings.

FIG. 1 is a schematic diagram of a concentration measuring contact whichis used in a method of measuring the concentration of concentrations ofspecific components in subjects of measurement in accordance with oneembodiment of the invention.

With this embodiment, one case will be described in which aconcentration of glucose, as a specific component in a subject ofmeasurement, is measured.

As a light source 1, a light source that emits mid-infrared light isused. In this embodiment, a SiC light source is used as the light source1. The SiC light source is particularly suitable for makingconcentration measurements for substances whose absorption wave numberis in the fingerprint region (mid-infrared region) of, for example, 1080cm⁻¹ and 1033 cm⁻¹.

As a material for a concentration measuring contact 2, is preferablyused a material which is capable of transmitting mid-infrared light,chemically stable and excellent in mechanical strength. In thisembodiment, germanium is used as the material for the concentrationmeasuring contact 2.

A contact portion 4 is brought into contact with a subject ofmeasurement. For example, when measuring the concentration of a glucosesolution, the glucose solution is dropped onto the contact portion 4 sothat the solution covers the entire surface of the contact portion 4.The glucose solution never overflows the contact portion 4, due to theeffect of its surface tension, and a suitable amount of solutionrequired for the concentration measurement is kept on the contactportion 4, which allows stable measurement of the glucose concentrationin the solution.

When the subject of measurement is a living body, the living body isbrought into tight contact with the contact portion 4. In this case, thearea of the portion which is in tight contact with the living body ispreferably 2 cm² or less. When the area is about 2 cm² or less, thecontact portion eats deeper into the living body and its contact withthe living body becomes much tighter, which allows stable measurements.As for the portion of the living body which is brought into tightcontact with the contact portion 4, the portion whose stratum corneum isthin is preferable, specifically proximal nail wall at the base of afinger-nail, lips and oral mucosa are preferable.

Preferably the shape of the contact portion 4 is, but not limited to,approximately circular. The reason is that when the subject ofmeasurement is a living body, the circular shape lessens the pain thesubject suffers at the time of measurement. More preferably theperiphery of the contact portion 4 is provided with a chamfered portionor a rounded portion, because providing such portions much lessens thepain of the subject.

As a photodetector 6, an MCT photodetector is used in this embodiment.

A polarizer 7 functions to take out a specific component of polarizedlight. In this embodiment, a wire grid polarizer is used in which aplurality of fine slits are provided. Rotating the polarizer 7 makes itpossible to arbitrarily set the component of polarized light thatreaches the photodetector 6 to s-polarized light or p-polarized light.The position of the polarizer 7 is not limited to the position shown inFIG. 1, it has only to be positioned on the optical path between thelight source 1 and the photodetector 6.

In FIG. 1, the direction shown by the solid line on the polarizer 7denotes the vibration direction of the s-polarized light component andthe direction shown by the broken line the vibration direction of thep-polarized light component. The polarizer 7 transmits light in the samevibration direction alone; therefore, measurement of the p-polarizedlight component, after measurement of the s-polarized light component inwhich the component of polarized light is set to the direction shown bythe solid line, needs to rotate the polarizer 7 at an angle of about 90degrees.

Providing, for example, spectroscopic means (not shown in the figure)between the light source 1 and the concentration measuring contact 2 ispreferable, because it allows the measurement of the wavelength-spectralcharacteristics of the specific component and obtaining the absorptioncharacteristics of the same at different wavelengths. The spectroscopy,FT-IR method, which uses an interferometer is particularly preferable asspectroscopic means, because it allows highly sensitive measurement.

Calculating means 8 calculates the concentration of a glucose solutionfrom the measurements obtained by the photodetector 6 utilizingcorrespondence information 9. As the calculating means 8, amicrocomputer or a personal computer made up of a CPU and a memory isused.

The calibration curve 9 is a collection of data obtained through thefollowing procedures: measuring in advance concentrations of glucosesolutions, whose concentrations are already known, by the method ofmeasuring the concentration of specific components in analytes inaccordance with the embodiment of the present invention; and getting themeasured results to have one to one correspondence to the knownconcentrations of glucose solutions. The calibration curve 9 is storedin, for example, the above described microcomputer or personal computerin advance.

The calibration curve 9 of this embodiment is one example ofcorrespondence information of this invention.

Then, the measurement flow of the concentration measuring method ofmeasuring a specific component contained in a subject of measurement inaccordance with this embodiment will be described with reference to FIG.2.

First, a glucose solution as a subject of measurement is set on thecontact portion of a concentration measuring contact (S1). In this step,background measurement using air or deionized water, which has beenrequired for the conventional concentration measuring method, is notneeded. Then, spectral characteristics of the glucose solution topolarized light are measured with the glucose solution set on thecontact portion (S2). As the spectral characteristics to polarizedlight, for example, spectral characteristics to s-polarized light andp-polarized light are measured. Then, in the calculating means 8,calculation is carried out using the measured value of the polarizedlight components and the concentration of glucose in the glucosesolution is calculated based on the obtained value (S3). As thecalculation, for example, the value, Ip/Is where Is represents themeasured value of the s-polarized light component and Ip the measuredvalue of the p-polarized value component, is calculated.

Then, a concentration measuring method using the concentration measuringcontact in accordance with this embodiment will be described withreference to FIG. 1.

A glucose solution, as a subject of measurement, is dropped on thesurface of the contact portion 4 so that the entire contact portion 4 isfilled with the solution. Light emitted by the light source 1 is enteredinto the contact portion 4 at an incident angle of θ so that itundergoes total reflection. At this time, evanescent light is oozed fromthe contact portion 4, transmitted in the glucose solution, returned tothe contact portion 4, passed through a light output portion 5 to itsoutside, and allowed to reach the photodetector 6 through the polarizer7.

The spectral characteristics of the glucose solution to the s-polarizedlight component is measured while setting the polarizer 7 in such amanner as to allow the light having a plane of vibration in thedirection shown by the solid line in the figure, that is, thes-polarized light to pass through the polarizer 7. Then the polarizer 7is rotated at an angle of 90 degrees and the spectral characteristics ofthe glucose solution to the p-polarized light component are measured.The measurement is completed at this point. The value, Ip/Is, iscalculated using the measured values Ip, Is at the respective wavenumbers and the concentration of glucose is calculated using the abovevalues and the calibration curve 9 obtained in advance.

In this measurement, it is preferable to set the incident angle θ of thelight entered into the contact portion 4 so that the value, z/λ,calculated using the following equation (1) becomes 0.25 or more.

$\begin{matrix}{\frac{Z}{\lambda} = \frac{1}{2\pi\sqrt{{n\; f^{2}\sin^{2}\theta} - {n\; c^{2}}}}} & \left( {{Mathematical}\mspace{14mu}{Equation}\mspace{14mu} 1} \right)\end{matrix}$wherein z represents the depth (unit: micron) to which the light enteredinto the contact portion oozes out of it, λ the wavelength (unit:micron) of the light entered into the contact portion, nf the refractiveindex of the contact portion, θ the incident angle of the light enteredinto the contact portion, and nc the refractive index of the subject ofmeasurement.

For example, in cases where the refractive index nc of the glucosesolution, as the subject of measurement, for the light with a wavelengthof about 9.6 microns is 1.24, if germanium, whose refractive index nf is4, is used for the contact portion, the incident light θ which satisfiesz/λ=0.25 is about 45 degrees. If light is entered into the contactportion at such an incident angle, the absorbance of the subject ofmeasurement differed largely depending on whether the incident light isthe s-polarized light or the p-polarized light. The concentration of aspecific component can be detected by the difference in absorbancecreated depending on whether the incident light is the s-polarized lightor the p-polarized light. Specifically, the s-polarized light oozes intothe subject of measurement only to a shallower portion, whereas thep-polarized light oozes into the subject of measurement to a deeperportion. And the s-polarized light is hardly affected by theconcentration of the specific component contained in the subject ofmeasurement. In other words, the measurement of the quantity of thes-polarized light corresponds to the measurement of background in theprior art and the measurement of the quantity of the p-polarized lightcorresponds to the measurement for the sample in the prior art. Thus,the concentration of the specific component can be detected by measuringthe quantities of the s-polarized light and the p-polarized light.

This method is effective when the incident angle of the light enteredinto the contact portion is about 45 degrees or less, but preferably theincident angle is larger than critical angle. If the incident angle issmaller than critical angle, the light does not satisfy the totalreflection requirements; as a result, the light is scattered in thesubject of measurement, which decreases the quantity of light returnedto the contact portion, and in addition, the optical path differencebetween the p-polarized light and the s-polarized light is decreased.Experiments showed that when z/λ=0.9 or more, in other words, when usinggermanium for the contact portion and setting the incident angle to 21degrees or 20 degrees, particularly satisfactory results were obtained,and when setting the incident angle to 19 degrees, much moresatisfactory results were obtained.

Generally, when making measurement using an FT-IR spectroscope, in manycases measuring operation is repeated several times while scanning thewavelength and the average measured value is calculated. This inventionis also effective in such a measuring method. For example, it ispreferable to make measurement for each polarized light componentseveral times and then calculate the average measured value.

The operations of measuring an s-polarized light component and measuringa p-polarized light component may be carried out alternately. In such acase, it is preferable to calculate Ip/Is, Is/Ip, log₁₀ (Ip/Is) or log₁₀(Is/Ip) based on the measured results of the s-polarized and p-polarizedlight components which are obtained at the respective measuring times inimmediate proximity to each other, because to do so makes it possible toprevent to the utmost the measured results from being affected by thechange in the light source and the photodetector with time.

It should be noted that this embodiment has been described taking thecase where a SiC light source is used as the light source 1, but thelight source is not limited to this. For example, tungsten is preferablyused as the light source 1. A quantum cascade laser is more preferablyused as the light source 1. These light sources are particularlysuitable for measuring the concentrations of substances, such asglucose, whose absorption wave numbers are in the fingerprint region(mid-infrared region) of about 1080 cm⁻¹ to 1033 cm⁻¹, like the casewhere a SiC light source is used.

Further, this embodiment has been described taking the case wheregermanium is used as the material for the concentration measuringcontact 2, but the material for the concentration measuring contact 2 isnot limited to this. Silicon, which is capable of transmittingmid-infrared light, chemically stable and excellent in mechanicalstrength, can also be used as the material for the concentrationmeasuring contact 2.

When using silicon as the material for the concentration measuringcontact 2, a silicon single crystal substrate is used which istransparent to light with a wavelength of 1.1 to 10 microns. Siliconhaving small content of impurities, such as boron and phosphorus, andhaving resistivity of 100 Ωcm or more is particularly preferable.Silicon having resistivity of 1500 Ωcm or more is much more preferable.The silicon having such high resistivity has high transmissivity atinfrared wavelength of about 9 to 10 microns, and it is preferably usedwhen measuring the concentration of substances, such as glucose, whoseabsorption region is in this wavelength band.

Preferably an antireflection film is provided on the surface of thelight input portion 3. As a material for the antireflection film,diamond-like carbon (DLC) or ZnSe is used. The thickness of theantireflection film is preferably 1.1 to 1.3 microns, more preferablyabout 1.2 microns.

Preferably an antireflection film is provided on the surface of thelight output portion 5, like the light input portion 3.

Further, this embodiment has been described taking the case where an MCTphotodetector is used as the photodetector 6, but the photodetector isnot limited to this. A pyroelectric sensor may also be used as thephotodetector 6.

The calibration curve 9 may be a table in which the measured results areallowed to have one to one correspondence to the known concentrations ofglucose solutions or a mathematical equation by which the measuredresults are allowed to have one to one correspondence to the knownconcentrations of glucose solutions.

Further, this embodiment has been described taking a case where a wiregrid polarizer is used as the polarizer 7, but the polarizer is notlimited to this. As the polarizer 7, an interference filter type ofpolarizer can also be used which transmits a p-polarized light componentand reflects an s-polarized light component.

FIG. 6 is a schematic diagram of a concentration measuring contact whichuses a polarizer 7 a, as an interference filter type of polarizer,instead of the polarizer 7 and is used in a concentration measuringmethod of measuring a specific component in a subject of measurement. InFIG. 6, the same parts as those of FIG. 1 are denoted by the samereference numerals and detailed description thereof will be omitted.

The polarizer 7 a functions to take out specific polarized lightcomponents just like the polarizer 7 of FIG. 1. The difference betweenthe polarizer 7 a and the polarizer 7 is in that the polarizer 7 areflects an s-polarized light component and transmits a p-polarizedlight component, as described above.

Accordingly, in FIG. 6, unlike FIG. 1, a photodetector 6 a of detectingthe quantity of a p-polarized light component, that is, lighttransmitted in the polarizer 7 a and a photodetector 6 b of detectingthe quantity of an s-polarized light component light, that is, lightreflected by the polarizer 7 a are arranged. As the photodetector 6 a, 6b, pyroelectric sensors are used. As the photodetector 6 a, 6 b, MCTphotodetectors may also be used.

With the concentration measuring contact shown in FIG. 6, sinces-polarized and p-polarized light components can be measured by thephotodetectors 6 a, 6 b at the same time, it is not necessary to measurethe spectral characteristics through the two-step procedure of:measuring the spectral characteristic of a glucose solution tos-polarized light component while setting the polarizer 7 so that ittransmits the s-polarized light component and then the polarizer 7 isrotated at an angle of 90 degrees, and measuring the spectralcharacteristic to p-polarized light component while keeping thepolarizer 7 in such a state. Accordingly, this embodiment gives effectof being less affected by the change of the light source 1.

Further, this embodiment has been described taking the case where aglucose solution is used as a subject of measurement, the subject ofmeasurement is not limited to this. The concentration measuring contactin accordance with this embodiment is useful for measuring theconcentration of glucose not only in a glucose solution, as a subject ofmeasurement, but also in blood plasma and in a living body. When thespecific component in a subject of measurement is a component other thanglucose, such as cholesterol, ethanol or the derivative of cholesterol,this embodiment can be effectively applied. However, the specificcomponent in a subject of measurement is changed, the wavelength oflight to be measured is also changed.

Specifically, when the specific component of a subject of measurement ischolesterol or the derivative of cholesterol, since the absorptionwavelength of cholesterol is 1500 nm or 1700 nm, a light source thatemits light with such a wavelength should be used as a light source 1 ora photodetector that detects light with such a wavelength should beused. When the specific component of a subject of measurement isethanol, since the absorption wave number of ethanol is 1240 cm⁻¹ or1400 cm⁻¹, a light source that emits light with such a wave numbershould be used as a light source or a photodetector that detects lightwith such a wave number should be used. When the specific component of asubject of measurement is different from the above described ones, if alight source that emits light with an absorption wave numbers of thespecific component of the subject of measurement is used or aphotodetector that detects light with such a wave number is used, theconcentration of the specific component in the subject of measurementcan be measured, like the above described components.

As described above, according to this embodiment, a concentrationmeasuring method of measuring specific component in a subject ofmeasurement is provided which enables stable and highly accurateconcentration measurement while avoiding the step of carrying outbackground measurement. The concentration measuring method of measuringa specific component of this invention is useful for measuring theconcentration of glucose not only in a glucose solution, but also inblood plasma, in a living body, etc.

EXAMPLE

The concentration of glucose in a glucose solution was measured using aconcentration measuring contact shown in FIG. 1. FIG. 3 illustratescharacteristic curves showing incident light wave number dependency ofthe values, Ip/Is, which were obtained by making measurement for glucosesolutions with different concentrations. In the measurement, glucosesolutions with different concentrations, 50, 100 and 200 mg/dl, wereused. And baseline correction was made so that the values, Ip/Is, becomezero at wave numbers of 1135 cm⁻¹ and 1000 cm⁻¹.

For example, when giving attention to the wave numbers 1076 cm and 1033cm⁻¹, it is seen that with the increase of the glucose concentration,the values, Ip/Is, are decreased and there is correlation between theglucose concentration and the value, Ip/Is.

FIG. 4 shows the relation between the values, Ip/Is, and the glucoseconcentration at a wavelength of 1033 cm⁻¹. It is seen from the figurethat there is straight line relationship and satisfactory correlationbetween the values, Ip/Is, and the glucose concentration. Thus, evenwhen background measurement, which is a step included in theconventional concentration measuring method, was not carried out, theglucose concentration could be calculated easily only by obtaining thevalue, Ip/Is, using the measured values Ip and Is. And the relationbetween the values, Ip/Is, and the glucose concentration shown in FIG. 4can be used as a calibration curve 9, which should obtained in advance.

FIG. 5 shows the relation between the values, Ip/Is, and the glucoseconcentration which are obtained using a light source whose quantity oflight is decreased by 10% compared with that of the light source withwhich the relation between the value, Ip/Is, and the glucoseconcentration shown in FIG. 4 is obtained. Comparing FIG. 4 with FIG. 5,it is seen that the Ip/Is—glucose concentration relations of both casesare substantially the same straight line. Thus, it is apparent thatobtaining the value, Ip/Is, like in this embodiment, makes it possibleto obtain glucose concentration with a high accuracy, even when thequantity of light from the light source is decreased due to its changewith time

This embodiment has been described taking the case where glucoseconcentration is obtained using the value, Ip/Is, the value used is notlimited to this. The same effect can be obtained when using the value,Is/Ip, log₁₀ (Ip/Is) or log₁₀ (Is/Ip).

INDUSTRIAL APPLICABILITY

As is apparent from the description so far, according to this invention,a concentration measuring apparatus, concentration measuring contactapparatus, concentration measuring calculating apparatus, andconcentration measuring method can be provided which enables stable andhighly accurate concentration measurement while avoiding the step ofcarrying out background measurement.

1. A concentration measuring apparatus, comprising: a concentrationmeasuring contact that is brought into contact with a subject ofmeasurement; a light source that emits light and enters the light intothe concentration measuring contact; a polarizer that takes outp-polarized and s-polarized light components from the light which ispassed through the concentration measuring contact into the subject ofmeasurement, transmitted in the subject of measurement, and returned tothe concentration measuring contact; a photodetector that determines atleast the quantities of the p-polarized and s-polarized light componentstaken out by the photodetector; and calculating means that calculatesthe concentration of a specific component contained in the subject ofmeasurement based on the determined results.
 2. The concentrationmeasuring apparatus according to claim 1, wherein the calculating meanscalculates the concentration of the specific component utilizingcorrespondence information obtained in advance that allows thedetermined results to have a one-to-one correspondence with theconcentrations of the specific component.
 3. The concentration measuringapparatus according to claim 1, wherein the concentration measuringcontact is an attenuated total reflection device and the light enteredinto the subject of measurement is evanescent light that oozes from theattenuated total reflection device.
 4. The concentration measuringapparatus according to claim 1, wherein the subject of measurement is aliving body tissue and the specific component is glucose, ethanol,cholesterol or a derivative of cholesterol.
 5. The concentrationmeasuring apparatus according to claim 1, wherein the calculating meanscarries out calculation according to the equation, log10 (Is/Ip) orlog10 (Ip/Is), where Ip represents the measured value of the quantity ofthe p-polarized light component and Is represents the measured value ofthe quantity of the s-polarized light component, and obtains theconcentration of the specific component based on the calculated value.6. The concentration measuring apparatus according to claim 1, whereinthe calculating means carries out calculation according to the equation,Ip/Is or Is/Ip, where Ip represents the measured value of the quantityof the p-polarized light component and Is represents the measured valueof the quantity of the s-polarized light component and obtains theconcentration of the specific component based on the calculated value.7. The concentration measuring apparatus according to claim 1, whereinthe photodetector measures the quantities of the p-polarized lightcomponent and the s-polarized light component alternately at least onetime or more for each, the calculating means selects, from among themeasured values measured by the photo detector, the measured value ofIp, the quantity of the p-polarized light component, and the measuredvalue of Is, the quantity of the s-polarized light component, the valuesbeing obtained at the respective measurement time points in immediateproximity to each other, carries out calculation using the selected Ipand Is values, and obtains the concentration of the specific componentbased on the calculated value.
 8. A concentration measuring method ofmeasuring a specific component contained in a subject of measurementcomprising: a contacting step of bringing the concentration measuringcontact into contact with the subject of measurement; a light enteringstep of entering light into the concentration measuring contact; ameasuring step of measuring at least the quantities of the p-polarizedlight component and the s-polarized light component of the light that ispassed through the concentration measuring contact into the subject ofmeasurement, transmitted in the subject of the measurement, and returnedto the concentration measuring contact; and a calculating step ofcalculating the concentration of the specific component contained in thesubject of measurement based on the determined results in the measuringstep.
 9. A concentration measuring contact apparatus including: aconcentration measuring contact that is brought into contact with asubject of measurement; a light source that emits light and enters thelight into the concentration measuring contact; a polarizer that takesout p-polarized and s-polarized light components of the light that ispassed through the concentration measuring contact into the subject ofmeasurement, transmitted in the subject of measurement, and returned tothe concentration measuring contact; and a photodetector that determinesat least the quantities of the p-polarized light component and thes-polarized light component taken out by the polarizer, wherein theconcentration of a specific component contained in the subject ofmeasurement is calculated by calculating means based on the determinedresults.
 10. A concentration measuring calculating apparatus including:calculating means that calculates the concentration of a specificcomponent contained in a subject of measurement based on determinedresults obtained by a concentration measuring contact apparatus whichincludes: a concentration measuring contact that is brought into contactwith the subject of measurement; a light source that emits light andenters the light into the concentration measuring contact; a polarizerthat takes out p-polarized and s-polarized light components of the lightthat is passed through the concentration measuring contact into thesubject of measurement, transmitted in the subject of measurement, andreturned to the concentration measuring contact; and a photodetectorthat determines at least the quantities of the p-polarized lightcomponent and the s-polarized light component taken out by thepolarizer.